The proposed research seeks to elucidate chemical, ultrastructural, and metabolic characteristics of the title subject. The mechanism of translocation of glycoprotein enzymes from the cytoplasm, through the plasma membrane, and into the periplasmic space will be studied in a model system involving Saccharomyces rouxii on which the principal investigators have provided much biochemical and ultrastructural background. The effects of the polyene antimycotic amphotericin B on Histoplasma capsulatum, the causative agent of Histoplasmosis, will be extended with particular interest in responses elicited indirectly on the vacuoles. The preliminary work on the ultrastructural localization of adenyl cyclase and phosphodiesterase in H. capsulatum will be extended and biochemical analyses on cyclic AMP levels will be obtained. There is great interest in possible changes in cyclic AMP concentration as effected by the above key enzymes and the relationship to dimorphism and the conversion also of microconidia into proliferating yeast cells. The metabolic inhibitors 5-thioglucose and thiotrehalose will be studied in Torulopsis glabrata and Candida albicans. Particular attention will be paid to glycogen turnover and metabolic pathways for glucose as well as the effects of the thioanalogs on viability of the test organisms. A long range goal of this research is to propose methods for inhibiting fungal cell growth in the compromised host.